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Journal article
Lymphotoxin beta receptor-mediated NF kappa B signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells
Journal of neuroinflammation, v 15(1), pp 49-49
20 Feb 2018
PMID: 29463313
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Lymphotoxin (LT) is a lymphokine mainly expressed in lymphocytes. LT alpha binds one or two membrane-associated LT beta to form LT alpha(2)beta(1) or LT alpha(1)beta(2) heterotrimers. The predominant LT alpha(1)beta(2) binds to LT beta receptor (LT beta R) primarily expressed in epithelial and stromal cells. Most studies on LT beta R signaling have focused on the organization, development, and maintenance of lymphoid tissues. However, the roles of LT beta R signaling in the nervous system, particularly in neurogenesis, remain unknown. Here, we investigated the role of LT beta R-mediated NF kappa B signaling in regulating neural lineage differentiation.
Methods: The C57BL/6J wild-type and GFAP-dnI kappa B alpha transgenic mice were used. Serum-free embryoid bodies were cultured from mouse embryonic stem cells and further induced into neural stem/progenitor cells (NSCs/NPCs). Primary neurospheres were cultured from embryonic and adult mouse brains followed by monolayer culture for amplification/passage. NF kappa B activation was determined by adenovirus-mediated NF kappa B-firefly-luciferase reporter assay and p65/RelB/p52 nuclear translocation assay. LT beta R mRNA expression was evaluated by quantitative RT-PCR and LT beta R protein expression was determined by immunohistochemistry and Western blot analysis. Multilabeled immunocytochemistry or immunohistochemistry followed by fluorescent confocal microscopy and quantitative analysis of neural lineage differentiation were performed. Graphing and statistical analysis were performed with GraphPad Prism software.
Results: In cultured NSCs/NPCs, LT alpha(1)beta(2) stimulation induced an activation of classical and non-classical NF kappa B signaling. The expression of LT beta R-like immunoreactivity in GFAP(+)/Sox2(+) NSCs was identified in well-established neurogenic zones of adult mouse brain. Quantitative RT-PCR and Western blot analysis validated the expression of LT beta R in cultured NSCs/NPCs and brain neurogenic regions. LT beta R expression was significantly increased during neural induction. LT alpha(1)beta(2) stimulation in cultured NSCs/NPCs promoted astroglial and oligodendrocytic lineage differentiation, but inhibited neuronal lineage differentiation. Astroglial NF kappa B inactivation in GFAP-dnI kappa B alpha transgenic mice rescued LT beta R-mediated abnormal phenotypes of cultured NSCs/NPCs.
Conclusion: This study provides the first evidence for the expression and function of LT beta R signaling in NSCs/NPCs. Activation of LT beta R signaling promotes glial lineage differentiation. Our results suggest that neurogenesis is regulated by the adaptive immunity and inflammatory responses.
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- Title
- Lymphotoxin beta receptor-mediated NF kappa B signaling promotes glial lineage differentiation and inhibits neuronal lineage differentiation in mouse brain neural stem/progenitor cells
- Creators
- Xiao Xiao - Temple UniversityRaj Putatunda - Temple UniversityYonggang Zhang - Temple UniversityPriya V. Soni - Temple UniversityFang Li - Temple UniversityTing Zhang - Temple UniversityMingyang Xin - Temple UniversityJin Jun Luo - Temple UniversityJohn R. Bethea - Drexel UniversityYuan Cheng - Second Affiliated Hospital of Chongqing Medical UniversityWenhui Hu - Temple University
- Publication Details
- Journal of neuroinflammation, v 15(1), pp 49-49
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- R01-MH101041; R01-DK075964 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01DK075964 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000425973800001
- Scopus ID
- 2-s2.0-85042522249
- Other Identifier
- 991019168042404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Neurosciences